Our research is broadly concerned with questions regarding bacterial-mucosal relationships in human tissues having an intact secretory immune system. We propose to examine the role of highly specific IgA proteases produced by Neisseria gonorrhoeae in the pathogenesis of infection. The studies will include separation of the IgAl and IgA2 subclasses in human colostrum, using lectin binding to peanut agglutinin, and evaluation of the role of each subclass in gonococcal immunity. We propose to isolate an IgA-protease negative strain of N. gonorrhoeae by mutation followed by recognition of such a strain using filter affinity techniques in vitro. A model of gonococcal-mucosal binding, human rectal grown in organ culture, will be used to evaluate the separated subclasses as adherence inhibitors and to explore the function of IgA protease at a relevant tissue site. We will also undertake a detailed study of the observed inhibition of IgA protease by human secretory IgA and plasma, attempting to localize the inhibitor among the plasma proteins and to characterize its mechanism; these studies will include assessment of anti-gonococcal activity in secretory IgA from which inhibitor to the enzyme has been removed. The hypothesis underlying the research is that secretory IgA antibody, microbial IgA protease and natural inhibitors to this enzyme all interact in the mucosal environment to influence the development and course of gonococcal disease.